Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions.
Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions.
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DOI：
10.1088/0031-9155/59/13/3465
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发表时间：
2014-07-07
影响因子：
3.5
通讯作者：
Porter TM
中科院分区：
文献类型：
--
作者：
Kopechek JA;Park EJ;Zhang YZ;Vykhodtseva NI;McDannold NJ;Porter TM
晚期肿瘤由于其大小和靠近关键血管结构而通常无法手术。高强度聚焦超声 (HIFU) 已被开发用于非侵入性热消融无法手术的实体瘤。然而，HIFU消融治疗的临床可行性受到治疗时间长（数小时）和所需高声强度的限制。研究表明，惯性空化可以通过产生宽带声发射来增强 HIFU 介导的加热，从而增加组织吸收并加速 HIFU 引起的加热。不幸的是，在肿瘤中引发惯性空化需要高强度并且可能是不可预测的。为了满足这一需求，开发了相移纳米乳液（PSNE）。 PSNE 由直径小于 200 nm 的脂质涂层液体全氟化碳液滴组成，从而允许通过渗漏的肿瘤脉管系统在肿瘤中被动积累。 PSNE 可以在肿瘤中汽化成微泡，从而使空化活性成核并增强 HIFU 介导的加热。在本研究中，对体内肌内兔 VX2 肿瘤进行 MR 引导的 HIFU 治疗，以评估汽化 PSNE 对声空化和 HIFU 介导的加热的影响。使用 1.5 MHz MR 兼容传感器传输 HIFU 脉冲 30 秒，并使用 650 kHz 环形水听器记录空化发射，同时使用 MR 测温法监测温度。 PSNE 注射后空化发射显着升高（P<0.05），这与增强的 HIFU 介导的肿瘤加热密切相关。注射PSNE后，超声处理引起的峰值温升显着升高（P<0.05）。例如，PSNE 注入在 5.2 W 声功率下实现的平均温度变化百分比为 46 ± 22%。结果表明，PSNE 形成空化，这与增强 HIFU 介导的肿瘤加热相关。这表明 PSNE 可能用于减少 HIFU 介导的加热所需的时间和/或声强度，从而提高 HIFU 热消融治疗的可行性和临床疗效。
Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 seconds using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650-kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P<0.05) after PSNE injection and this was well correlated with enhanced HIFU-mediated heating in tumors. The peak temperature rise induced by sonication was significantly higher (P<0.05) after PSNE injection. For example, the mean percent change in temperature achieved at 5.2 W of acoustic power was 46 ± 22% with PSNE injection. The results indicate that PSNE nucleates cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could potentially be used to reduce the time and/or acoustic intensity required for HIFU-mediated heating, thereby increasing the feasibility and clinical efficacy of HIFU thermal ablation therapy.
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